chance ER+/PR+ HER2- might benefit from immunotherapies?

what is a "cold tumor"?

Thank You Bljen.  So  it's better to have a hot tumor

Skyfly,

Do you mean immunotherapy trials for vanilla MBC, hormone receptor positive, Her2 negative?

Funny you should ask. After being all thrilled about that trial at MSK,it turns out that I might not be producing enough mesothelin to be included in the trial. The blood test from Mayo had me at 1, but MSK's test has me at .7. Blurg.

The real key to this trial door is whether the tumor produces enough mesothelin. As per Dr. Modi, you can have it in your bloodstream from the tumor, but your mileage may vary as to your actual tumor being chock full of mesothelin. Some people's immune systems destroy the mesothelin once it enter the bloodstream - I think.

That's what I'm waiting on. To find out what my actual tumor is up to. According to the nurse in charge of the trial, it will be at least a week more before the test results come back in.

Skyfly, that's my long winded way of telling you that the most viable trial I have found for ER/PR+, Her2- (this one), is very mesothelin dependent. In their defense, they are targeting mesothelin, so if you aren't making enough of it, it's rather a waste of their time and money.

There's a trial in Virginia, https://clinicaltrials.gov/ct2/show/NCT03272334, that is targeting Her2 stem cells, which everyone has. It's only when they grow up that they count as Her2+. They are getting a PFS of about 24 months for vanilla MBC, but 57 months for Her2+. Still, I wouldn't sneeze at two years.

Here's another interesting one for vanilla MBC, "Pembrolizumab and Carboplatin in Treating Patients With Circulating Tumor Cells Positive Metastatic Breast Cancer, NCT03213041."

Here's the summary: "The purpose of the study is to evaluate the impact on progression-free survival (PFS) with the combination carboplatin - pembrolizumab in patients with CTC (circulating tumor cells) positive, HER2 negative metastatic breast cancer previously treated with anthracyclines and taxanes. Previous studies have indicated that recurrent breast cancers are more resistant to chemotherapy and maybe associated with a weak immune system. This study is investigating the use of an immune therapy drug, pembrolizumab, that has the ability to restore the capacity of controlling and killing cancer cells of an important component of your immune system called T-cells. Pembrolizumab has been found effective in other types of cancer and has already been approved by FDA for those indications, but the efficacy in breast cancer is still unknown. In this study, pembrolizumab will be combined with chemotherapy to increase the cancer cell killing. There is no control or placebo treatment in this study." The bolding is mine, to point out that being heavily pre-treated doesn't seem to be exclusionary, and everyone gets the drugs. The exclusionary criteria most likely to bite one on the fanny: "Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent."

The next one that looks good is, "Type I-Polarized Autologus Dendritic Cell Vaccine With Tumor Blood Vessel Antigen-Derived Peptides in Metastatic Breast Cancer Patients, NCT02479230".

"The vaccine is made up of natural cells found in the blood, called dendritic cells, and peptides, or small fragments of protein which are loaded onto the dendritic cells. This combination may help activate the immune system against stromal cells, which are cells that help cancer cells survive in the body." They use the Gemcitabine hydrochloride to tamp down the patient's immune system before they administer the vaccine, so that it can get right to work, and - maybe - not be gobbled down by the patient's own immune system. It's not CAR-T, but is a very interesting approach.

Stuff that could exclude you: Patients must be human leukocyte antigen (HLA)-A2+. Good news: There is no limit to the number of prior systemic treatment regimens.

I'd have to look, but I think I'm the wrong kind of HLA, from having a go at a trial at the Roswell Institute.

Because I'm getting tired, I'll just give the NCI # on this one: NCT02453620. It's a novel combination of immunotherapy drugs, and an easy read. It's not personalized, like CAR-T or vaccines.

This trial, NCT02188745, is to see if they can't resensitize hormone sensitive tumors that start behaving like triple negative, leaving the patient eligible for more endocrine therapies. For example, I'm 95% ER+, 80% PR+, but I've have gotten no use from any of the endocrine therapies, with the exception of Faslodex, which I did great on. To be honest, this is an approach you should be able to sweet talk your MO into, but I'm glad they are getting reproducible data on the process.

I realize that I've twisted your question from if I've read anything interesting about advances in immunotherapy to what trials would be good for ER/PR+, Her2- people. Here are some articles I was so moved as to keep handy:

https://medicalxpress.com/news/2019-04-relapse-can...

https://www.sciencedaily.com/releases/2019/04/1904...

https://medicalxpress.com/news/2019-02-potentially...

https://www.sciencemag.org/news/2017/12/old-drug-a...

Hope that helps.

Jennifer

Skyfly,

The problem with solid tumors and immunotherapy is finding the right target. You have to look for something that exists within your cancer that is fairly unique to the cancer and not to the rest of your body. That little problem is what caused those few deaths in the beginning era of CAR-T (read up on cytokine storms). Chemo has the same problem in that it kills off rapidly dividing cells, like cancer cells, but also like bone marrow cells, and hair follicle cells.

The infusion center I go to just got a machine that circulates cold water over a patient's scalp to mitigate baldness. I refused it because skull mets are real, and I haven't read enough data that this protocol doesn't affect the skull. Plus, I wish they had spent the money on the same machine, but for hands and feet because neuropathy is a big deal. But, guess what? They don't even make a machine that does that, as per the infusion center manager. What the what? If so, it means that vanity triumphs over daily living skills. Walking remains more important than hair for me.

Immunotherapies are working well for liquid cancers (ie: blood borne), but are having problems addressing a solid tumor. It likes to kill off the outside of a lesion. I have to work harder on getting a biopsy of my liver monster that demonstrates that its center is necrotic, meaning that my immune system is attacking the tumor, but then the lesion just continues to build from the necrotic tissue, like a scaffold. It means something good, but the data escapes me now. I'll get back to you about it, as soon as I re-find it.

So far, the Triple Negatives and the Her2+ patients seem to have a boatload of cool genomic mutations in their cancers to target with immunotherapy. We vanilla MBCers, not so much.

The two targets that I have seen are mesothelin and HLA type 2. I'm waiting on the mesothelin results, and didn't not have the correct HLA type when tested at Roswell Park for a trial there. I have asked my MO for a retest on the HLA, as it is the target for at least 2 dendritic cell vaccines that I have read about.

How is your Mom doing?

Jennifer

edited because grammar is hard, my dog is sick, and I'm so tired.